When PD-L1 or PD-L2 binds to PD-1 expressed on the surface of a T cell, the T cell receives an inhibitory signal, causing it to suppress T-cell proliferation and cytokine production, and thereby inhibiting the T-cell-associated immune response 7, 8. The key ligands of PD-1 include PD-L1 (also known as CD274, B7-H1) and PD-L2 (also known as CD273, B7-DC) these ligands are expressed by immune cells and can be induced in many different tissues 4, 5, 6. PD-1 is an important immune checkpoint molecule, which inhibits the functions of CD4 + and CD8 + T cells in the tumor microenvironment 2, 3. Programmed cell death protein 1 (PD-1 also known as CD279), a member of the T-cell receptor CD28 family, is expressed on the surfaces of a variety of immune cells, including monocytes, T cells, and B cells 1. These results suggest MW11-h317 as a therapeutic monoclonal antibody of PD-1 glycosylation-targeting which may become efficient alternative for cancer therapy. The unique glycan epitope in PD-1 to MW11-h317 is different from the first two approved clinical PD-1 antibodies, nivolumab and pembrolizumab. Crystal structure of PD-1/MW11-h317 Fab complex reveals that both the loops and glycosylation of PD-1 are involved in recognition and binding, in which Asn58 glycosylation plays a critical role. MW11-h317 can effectively induce T-cell-mediated immune response and inhibit tumor growth in mouse model. Here we show that MW11-h317, an anti-PD-1 monoclonal antibody, displays high affinity for PD-1 and blocks PD-1 interactions with PD-L1/L2. Monoclonal antibody-based drugs targeting PD-1 pathway have exhibited great promise in cancer therapy. Blocking the interaction of PD-1 and its ligands PD-L1/ L2 is able to active T-cell-mediated antitumor response.
Programmed cell death 1 (PD-1) is inhibitory receptor and immune checkpoint protein.